- Review Article
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Molecular insights into transgenerational non-genetic inheritance of acquired behaviours
Nature Reviews Geneticsvolume 16, pages641–652 (2015)Cite this article
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Key Points
Environmental factors can lead to heritable non-genetic changes in the mammalian germ line that affect behaviour in the offspring across several generations. These changes influence behaviours related to human neuropsychiatric disease and higher cognitive functions.
Experimental strategies in laboratory rodents can be used to test the germline dependence of heritable changes in behaviour.
Novel non-genetic mechanisms such as epigenetic marks and non-coding RNAs have emerged as likely vectors for germline transmission.
The routes and mechanisms by which environmental factors can affect non-genetic factors in germ cells are discussed.
Major questions remain to be addressed, including the identification of non-genetic modifications that are altered by the environment in germ cells, the mechanisms of their induction and maintenance during development and adulthood, and the way in which they affect behaviour.
Abstract
Behavioural traits in mammals are influenced by environmental factors, which can interact with the genome and modulate its activity by complex molecular interplay. Environmental experiences can modify social, emotional and cognitive behaviours during an individual's lifetime, and result in acquired behavioural traits that can be transmitted to subsequent generations. This Review discusses the concept of, and experimental support for, non-genetic transgenerational inheritance of acquired traits involving the germ line in mammals. Possible mechanisms of induction and maintenance during development and adulthood are considered along with an interpretation of recent findings showing the involvement of epigenetic modifications and non-coding RNAs in male germ cells.
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Acknowledgements
The Mansuy laboratory is supported primarily by the University of Zürich, ETH Zürich and the Swiss National Science Foundation. The authors thank S. Steinbacher for help with drafting illustrations, K. Gapp for critically reading the manuscript and the anonymous reviewers for their constructive comments.
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Laboratory of Neuroepigenetics, University of Zürich and ETH Zürich, Center for Neuroscience Zürich, Brain Research Institute, Winterthurerstrasse 190, Zürich, CH-8057, Switzerland
Johannes Bohacek & Isabelle M. Mansuy
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Glossary
- DNA methylation
Involves the transfer of a methyl residue to cytosine (5-methylcytosine) in CpG dinucleotides.
- DNA hydroxymethylation
Results from oxidation of 5-methylcytosine into 5-hydroxymethylcytosine by ten-eleven translocation dioxygenases (TETs).
- Post-translational modifications
(PTMs). Covalent modifications such as methylation (mono, bi or tri), acetylation and phosphorylation on specific histone residues (primarily lysine, arginine and serine).
- Non-coding RNAs
(ncRNAs). Functional RNA molecules that are not translated into proteins. ncRNAs can regulate gene transcription by DNA binding and prevent translation by mRNA silencing or degradation. Major ncRNAs include the small ncRNAs (microRNAs, small interfering RNAs, PIWI-interacting RNAs and small nucleolar RNAs) and long ncRNAs.
- Nucleosome positioning
The location of nucleosomes on the chromatin. It is non-random and dynamic, and affects gene regulation.
- Behavioural despair
When an animal stops struggling to escape adverse conditions, such as being suspended by the tail (tail suspension test) or placed in a small container of cold water (forced swim test). Struggling or immobility can, however, sometimes reflect the survival response or adaptive learning depending on the task conditions.
- Environmental enrichment
The supplementation of an individual's living conditions by social, sensory and physical stimuli.
- Perseveration
The repetition of the same response in the absence of any adjustment to changing requirements of a task.
- Operant conditioning tasks
Tasks that involve behavioural learning through repeated reinforcement or punishment.
- Paramutation
The transfer of epigenetic information from one allele of a gene to the other allele to establish a heritable state of gene expression.
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Bohacek, J., Mansuy, I. Molecular insights into transgenerational non-genetic inheritance of acquired behaviours.Nat Rev Genet16, 641–652 (2015). https://doi.org/10.1038/nrg3964
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